The long-term objective of this projjct is to understand the genetic and epigenetic mechanisms by which the tumor cell regulates the expression of its tumor-associated antigens. Antigenic variants of murine lymphomas growing in tissue culture are being used to study the genetics of several model normal and tumor-associated cell surface antigens. Particular emphasis is being placed on understanding the Thy-1 and TL antigens. Mutant cell lines which do not express these antigens on their cell surface are being isolated by cytotoxic immunoselection and characterized using a combination of somatic genetic and biochemical approaches. Hybrids between cell lines expressing Thy-1 and cell lines representing cell types which normally do not express Thy-1 are also under study. By this means the number and natre of the genes involved in the biosynthesis of a particular cell surface molecule are being defined.